Lee Yeji, Lee Changyeol, Lee Sang-Han, Lee Yoon-Jin
Department of Biochemistry, College of Medicine, Soonchunhyang University, Cheonan 31511, Republic of Korea.
Life (Basel). 2025 May 22;15(6):836. doi: 10.3390/life15060836.
Butein (3,4,2',4'-tetrahydroxycalone) is a chalcone derivative and plant polyphenol extracted from . Butein has an open C-ring structure and a variety of biological activities. Molecular mechanisms by which butein could affect cell viability, ROS levels, mitochondrial function, apoptosis, and necrosis in prostate cancer cells were investigated using 2D monolayer and 3D sphere culture systems. Cytotoxicity and cell cycle monitoring showed that butein treatment decreased cell viability and increased peaks of sub-G/G and G/M phases analyzed by flow cytometry. These changes were observed with a concurrent induction of DNA damage, apoptosis, and necrosis. Although 3D spheres treated with butein showed decreased cell viability, they were slightly more resistant than cells in 2D cultures. This phenomenon was accompanied by an increase in mediators of apoptosis and necrosis. Monitoring changes of apoptosis-related proteins via Western blot showed that butein decreased caspase-3, PARP, and Bcl-2, but increased Bax. Meanwhile, butein increased levels of p-receptor interacting serine/threonine-protein kinase 3 (p-RIP3) and p-mixed lineage kinase domain-like kinase (p-MLKL) known to be mediators of necrosis. Overall, our data suggest that butein can induce apoptosis and necrosis of prostate cancer cells by regulating pro- and anti-apoptotic proteins via ROS. Thus, butein might be a potential agent for treating prostate cancer.
白杨素（3,4,2',4'-四羟基查耳酮）是一种查耳酮衍生物和从……中提取的植物多酚。白杨素具有开放的C环结构和多种生物活性。使用二维单层和三维球体培养系统研究了白杨素影响前列腺癌细胞活力、活性氧水平、线粒体功能、凋亡和坏死的分子机制。细胞毒性和细胞周期监测表明，白杨素处理降低了细胞活力，并增加了通过流式细胞术分析的亚G/G期和G/M期的峰值。这些变化伴随着DNA损伤、凋亡和坏死的同时诱导。虽然用白杨素处理的三维球体显示细胞活力下降，但它们比二维培养中的细胞略有抗性。这种现象伴随着凋亡和坏死介质的增加。通过蛋白质印迹监测凋亡相关蛋白的变化表明，白杨素降低了半胱天冬酶-3、聚（ADP-核糖）聚合酶和Bcl-2，但增加了Bax。同时，白杨素增加了已知为坏死介质的磷酸化受体相互作用丝氨酸/苏氨酸蛋白激酶3（p-RIP3）和磷酸化混合谱系激酶结构域样激酶（p-MLKL）的水平。总体而言，我们的数据表明，白杨素可通过活性氧调节促凋亡和抗凋亡蛋白来诱导前列腺癌细胞的凋亡和坏死。因此，白杨素可能是治疗前列腺癌的潜在药物。
